1. Area of the Background
This invention is generally in the area of urology and more specifically in improved treatment and outcome for radical prostatectomy surgery.
2. Description of the Background
Low testosterone level (“andropause”, androgen deficiency of the aging male [ADAM] or hypogonadism) has an estimated prevalence of 2 to 4 million men in the United States of which only 5% receive treatment. [1] Testosterone deficiency can be linked to premature mortality and to a number of systemic diseases such as sexual disorders, diabetes, cardiovascular disease and metabolic syndrome. [2] Symptoms include decreased libido, depression, decreased muscle mass and bone density, anemia and lack of energy. [3] Total testosterone starts to decrease at age 40 years at a rate of approximately 1% (3.2 ng/dl) per year. [4] Mulligan et al. found the prevalence of hypogonadism was 38.7% in men 45 years and older presenting to primary care offices. [5] In addition to general health issues we have also confirmed earlier publications for an oncological effect. Our data (discussed below) confirm earlier reports that lower androgen levels are associated with higher grade Prostate Cancers which have a greater risk of extraprostatic extension and positive surgical margins.
In 1941, Huggins and Hodges showed that removal of the testicles (which are the primary sources of testosterone) resulted in regression of prostate cancer. [9] Since that report it has been considered taboo to offer men with history of prostate cancer any form of testosterone supplementation because of concerns such supplementation would result in recurrence of disease. [10] Although the majority of prostate cancer patients treated with local therapy is cured, approximately 15% to 40% will experience a biochemical PSA recurrence. [19 and 20] However, several recent clinical studies have shown testosterone replacement in men after a radical prostatectomy increased testosterone levels without increasing prostate specific antigen (PSA). [11, 12 and 13] These studies in effect challenge the idea that testosterone replacement is unsafe in men with low testosterone and a history of radical prostatectomy for prostate cancer. However, it should be kept in mind that these studies are based on small numbers of men (7, 10 and 57) and over short time periods (13 and 19 months).
Thus, the U.S. Food and Drug Administration continues to mandate that testosterone package inserts state that testosterone is contraindicated in men who have a history of prostate cancer. [17] The 2002 Third International Consensus Consultation on Prostate Cancer recommends that patients with prostate cancer never receive testosterone supplementation because of the fear that testosterone replacement therapy following a radical prostatectomy might promote recurrence from residual prostate cancer. [18]
Testosterone supplementation may also have side effects such as overproduction of red blood cells which could lead to clotting problems, liver problems, and exacerbation of sleep apnea as well as side local effects at the site of administration.
Nevertheless, testosterone supplementation has been shown to counteract the negative effects of testosterone deficiency by enhancing sexual function, reversing depression, increasing bone mineral density and fat-free body mass, stimulating production of red blood cells and improving strength, energy, cognition and mood. [6-8] The studies mentioned above demonstrate that the use of testosterone supplementation is not associated with recurrence of prostate cancer. In fact, low testosterone is associated with an increased risk of prostate cancer [14] and with more aggressive and higher grade prostate cancer. [15] In addition, PSA values have not been shown to increase significantly after testosterone replacement therapy. [16]